MTHFR genetic polymorphism as a risk factor in Egyptian mothers
with Down syndrome children

Affiliations: Department of Research on Children with Special Needs,
National Research Center, Cairo, Egypt | Department of Biomedical Technology, National Research
Center, Cairo, Egypt | Department of Nutrition and Food Science, National
Research Center, Cairo, Egypt

Abstract: Recent reports linking Down syndrome (DS) to maternal polymorphisms
at the methylenetetrahydrofolate reductase (MTHFR) gene locus have
generated great interest among investigators in the field. The present study
aimed at evaluation of MTHFR 677C/T and 1298A/C polymorphisms in the
MTHFR gene as maternal risk factors for DS. Forty two mothers of proven DS
outcomes and forty eight control mothers with normal offspring were included.
Complete medical and nutritional histories for all mothers were taken with
special emphasis on folate intake. Folic acid intake from food or vitamin
supplements was significantly low (below the Recommended Daily Allowance) in
the group of case mothers compared to control mothers. Frequencies of
MTHFR 677T and MTHFR 1298C alleles were significantly higher among case
mothers (32.1% and 57.1%, respectively) compared to control mothers
(18.7% and 32.3%, respectively). Heterozygous and homozygous genotype
frequencies of MTHFR at position 677 (CT and TT) were higher among case
mothers than controls (40.5% versus 25% and 11.9% versus 6.2%,
respectively) with an odds ratio of 2.34 (95% confidence interval [CI]
0.93–5.89) and 2.75 (95% CI 0.95–12.77), respectively. Interestingly, the
homozygous genotype frequency (CC) at position 1298 was significantly higher in
case mothers than in controls (33.3% versus 2.1% respectively) with an
odds ratio of 31.5 (95% CI 3.51 to 282.33) indicating that this polymorphism
may have more genetic impact than 677 polymorphism. Heterozygous genotype (AC)
did not show significant difference between the two groups. We here report on
the first pilot study of the possible genetic association between DS and
MTHFR 1298A/C genotypes among Egyptians. Further extended studies are
recommended to confirm the present work.